Borrelia burgdorferi Strain-Specific Differences in Mouse Infectivity and Pathology

Lyme disease (LD), caused by infection with the tick-borne bacteria, <i>Borrelia burgdorferi</i>, is associated with a wide array of symptoms in human patients. Variations in clinical manifestations are thought to be influenced by genetic differences among <i>B. burgdorferi</i> strains. In this study, we evaluated the infectivity, tissue bacterial load, pathology, and immunogenicity of five strains of <i>B. burgdorferi</i> sensu stricto (297 Ah130, Bb16-54, B31-A3, Bb16-126, JD1) in female C3H/HeN mice at three infectious doses (10⁴, 10⁵, 10⁶ spirochetes). We found that strains Bb16-126 and JD1 were the most infectious, resulting in 100% infection across all the tested doses. Strain Bb16-126 caused the highest bacterial burden in the heart tissue and significant carditis, whereas JD1 exhibited the lowest spirochete load in the heart and minimal carditis. In comparison, strain B31-A3 demonstrated the highest abundance in the tibiotarsal joint. Infection with all the strains induced severe lymph node hyperplasia, with JD1 producing the greatest increase in cellularity. Using a diagnostic C6 peptide ELISA, all the strains induced significant anti-C6 IgM and IgG antibody titers at 14 days post-infection; however, strain B31-A3 elicited the highest anti-C6 IgM titers. Our findings demonstrate the importance of strain diversity in shaping <i>B. burgdorferi</i> pathogenesis in a mouse model and provide insights for developing strain-specific diagnostic, therapeutic, and vaccine strategies.